Our earlier studies first demonstrated that rapid discontinuation of lithium is followed by major increases in early risks of recurrences of mania, depression and suicide in bipolar disorder patients that are much less following gradual discontinuation. We also found evidence of similar effects of rapid vs. gradual discontinuation of antipsychotic agents in schizophrenia patients. Risk of relapse or recurrence in major depression is much higher after discontinuing vs. during antidepressant treatment, and abrupt discontinuation of some antidepressants can induce physiological withdrawal reactions. However, possible later impact of rapidly discontinuing antidepressants on risk or time to recurrence of new major depressive episodes has not been adequately studied. We hypothesize that risk and latency to recurrences of depression are greater/shorter after abrupt or rapid than gradual discontinuation of antidepressants, following recovery from an index episode of major depression. This hypothesis will be tested with a large computerized database of nearly 500 major affective disorder patients (that will be increased to approximately 1000 subjects) evaluated and followed for an average of 5 years in a collaborating mood disorder research clinic. Using survival-analysis with covariates, we will compare latency from antidepressant discontinuation to the onset of a first new episode of major depression. We will also compare episode counts, rates, durations, and wellness-intervals in subjects prior to psychiatric treatment and outcome measures following antidepressant discontinuation. Secondary analyses will compare selected demographic, clinical, and treatment factors among patients discontinuing antidepressants rapidly vs. gradually vs. those continuing antidepressant treatment, and will consider unipolar depressive vs. bipolar depressive subjects separately. The findings expected should contribute to improved safety of antidepressant treatment and reduced morbid and mortal risks following its discontinuation. [unreadable] [unreadable]